Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans

Nat Commun. 2021 Mar 12;12(1):1622. doi: 10.1038/s41467-021-21834-9.

Abstract

Our mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes
  • Genetic Therapy / methods
  • Hematopoietic Stem Cells
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / physiology*
  • Lymphocytes / physiology*
  • Lymphoid Progenitor Cells / physiology*
  • Mutagenesis
  • Myeloid Cells / physiology
  • Proto-Oncogenes / genetics
  • Proto-Oncogenes / physiology
  • T-Lymphocytes / physiology*

Substances

  • Interferon-gamma